title: Substituted quinazolines, part 3. Synthesis, in vitro antitumor activity and molecular modeling study of certain 2-thieno-4(3H)-quinazolinone analogs.
abstract: The synthesis of some new 2-thieno-4(3H)-quinazolinone derivatives and their biological evaluation as antitumor agents using the National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Compounds 2-(2-thienylcarbonylamino)-5-iodo-N-(4-hydroxyphenyl)-benzamide (16), 2-(2-thieno)-6-iodo-3-phenylamino-3,4-dihydro-quina-zolin-4-one (26), and 2-(2-thieno)-4-[4-sulfonamidobenzylamino]-6-iodo-quinazoline (42), with GI(50) values of 12.7, 10.3, 16.9 microM, respectively, proved to be the most active members in this study, as compared to the known drug 5-FU. Conformational analysis of the most active molecules using molecular modeling and QSAR techniques enabled the understanding of the pharmacophoric requirements for 2-thieno-quinzolinone derivatives as antitumor agents. These three quinazolinone analogs (16, 26, 42) could be considered as useful templates for future development to obtain more potent antitumor agents.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
authors.forename: Abdulrahman M
authors.initials: AM
authors.lastname: Al-Obaid
authors.forename: Sami G
authors.initials: SG
authors.lastname: Abdel-Hamide
authors.forename: Hassan A
authors.initials: HA
authors.lastname: El-Kashef
authors.forename: Alaa A-M
authors.initials: AA
authors.lastname: Abdel-Aziz
authors.forename: Adel S
authors.initials: AS
authors.lastname: El-Azab
authors.forename: Hamad A
authors.initials: HA
authors.lastname: Al-Khamees
authors.forename: Hussein I
authors.initials: HI
authors.lastname: El-Subbagh
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines